Previous studies of short-term plasticity in central nervous systems synapses have largely focused on average synaptic properties. In this study, we use recordings from putative single synaptic release sites in hippocampal slices to show that significant heterogeneity exists in facilitation and depletion among synapses. In particular, the amount of paired-pulse facilitation is inversely related to the initial release probability of the synapse. We also examined depletion at individual synapses using high frequency stimulation, and estimated the size of the readily releasable vesicle pool, which averaged 5.0 ± 3.0 quanta (n = 13 synapses). In addition, these experiments demonstrate that the release probability at a synapse is directly correlated with the size of its readily releasable vesicle pool.